title: Donor brain death significantly interferes with tolerance induction protocols.
abstract: Studies in rodents showed that antibodies are able to induce tolerance of allografts. As clinical results are unsatisfactory and deceased donors are still the main source of organ transplants, we investigated whether donor brain-death impacts on tolerance induction after experimental kidney transplantation. Anti-CD4 monoclonal antibodies (RIB 5/2; 2.5 mg/kg x 5 days) treated and untreated recipients of brain-dead donor grafts were compared with RIB 5/2 treated and untreated recipients of living donor grafts (F344-to-Lewis). All recipients received low-dose CsA (1.5 mg/kg x 10 days). Kidneys were recovered 4, 16 and 40 weeks after transplantation and examined by morphology, immunohistology and flow cytometry. Renal function was monitored monthly. RIB 5/2 treatment significantly decreased proteinuria in recipients of living donor allografts when compared with living donor controls. After 40 weeks, inflammatory cell infiltration and MHC class II expression were reduced while morphologic alterations were minimal. In contrast, treatment of brain-dead graft recipients had no impact on graft function. Structural changes and graft infiltration were comparable to brain-dead donor controls at all time points. RIB 5/2 treatment significantly improved graft function in recipients of living donor grafts; however, it was not effective in recipients of brain-dead donor organs.
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, Charité, Campus Virchow Clinic, Universitätsmedizin Berlin, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Francuski
authors.forename: Anja
authors.initials: A
authors.lastname: Reutzel-Selke
authors.forename: Sascha
authors.initials: S
authors.lastname: Weiss
authors.forename: Andreas
authors.initials: A
authors.lastname: Pascher
authors.forename: Anke
authors.initials: A
authors.lastname: Jurisch
authors.forename: Frank
authors.initials: F
authors.lastname: Ulrich
authors.forename: Guido
authors.initials: G
authors.lastname: Schumacher
authors.forename: Wladimir
authors.initials: W
authors.lastname: Faber
authors.forename: Sven
authors.initials: S
authors.lastname: Kohler
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001926:Brain Death / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D023001:Transplantation Tolerance
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens